EXCHANGE BETWEEN BICYCLO(2,2,1)HE;PrANE AND &BUTYL CHLORIDE
Feb., 1946
solution was then diluted with 50 cc. of water and acidified with 20 cc. of 3 N hydrochloric acid solution. There was obtained 5.0 g. of solid of indefinite melting point. This was recrystallized from 200 cc. of aqueous ethanol (1 : 1). Four grams (82%) of well-formed needles was obtained. Samples melted a t 186-187' (uncor.) with much preshrinking. The melting point given by Snapper and Grunbaum' is 179 '. The acid was readily and completely soluble in warm sodium bicarbonate solution (compare Fischer and Lipschit26 for behavior of a related acid and ester) and was not appreciably soluble in chloroform. A sample of the compound failed to give a ninhydrin test. In contrast to this behavior, both diiodotyrosine and the methyl ether of tyro:;ine6 gave positive ninhydrin reactions. Anal. Calcd. for ClaH130&Iz (537): X, 2.6. Found: S, 2.5; equivalent wt. by titration (methyl red), 536 f 1. (5) Fischer and Lipsrhitz, Ber., 48, 374 (1913). (6) Behr and Clarke. THIS JOURNAL, 54, 1630 (IR:iZ!)
CONTRIBUTION
FROM THE
195
4-10.9" * 0.3' for 0.607 g. dissolved in 0.5 N sodium hydroxide solution to 10.0 cc. After a second recrystallization, [ayIDn = +10.6 f 0.7' for 0.671 g. dissolved in 0.5 N sodium hydroxide solution to 10.0 cc.
Thanks are due Miss Velma Ladwig and Mr. Luther Eggman for Kjeldahl analyses.
Summary The synthesis of a number of derivatives of diiodotyrosine for testing as radio-opaque pharmaceutical compounds, is described. Details are given for the conversion of diiodotyrosine t o Nbenzoyldiiodotyrosine through some of these intermediates in better than 60% over-all yield. AMES,IOWA
RECEIVED OCTOBER 4, 1946
RESEARCH LABORATORIES O F UNIVERSAL OIL PRODUCTS COMPAKY]
The Exchange of Hydrogen and Chlorine between Bicyclo(2,2,l)heptane and &Butyl Chloride BY LOUISSCHMERLING The hydrogen--chlorine exchange reaction' of bicyclo(2,2,l)heptane (also called norcamphane) with t-butyl chloride was investigated because it seemed to offer a convenient means for preparing the tertiary chloride, l-&lorobicyclo(%,2,l)heptane (I), and thence (by condensation with olefins*) bicycloheptylalkyl chlorides containing quaternary carbon atoms.
c1 I
H H?C/T\CHCl,
H,C/f\CH:
I
?H!
CH? 1
~
H,c,L,CH. I
H I1
Bartlett, Condon and Schneiderl reported that poorly characterized products were obtained by the reaction of bicyclo(2,2,l)heptane with alkyl halides in the presence of aluminum chloride or aluminum bromide. Their general procedure consisted in shaking a mixture of the reactants and the catalyst a t room temperature in a separatory funnel for a period of time varying from ten seconds t o several minutes and then stopping the reaction either by separating the catalyst layer or by adding water. I n the present investigation i t was found that smooth transfer of chlorine from t-butyl chloride t o bicycloheptane can be accomplished in the presence of aluminum chloride by using lower reaction temperatures (about 0') and longer contact times (thirty to sixty minutes).
Chlorobicycloheptane was obtained in 22-24% of the theoretical yield based on the bicycloheptane charged or in 74-84y0 yield based on unrecovered bicycloheptane. However, the chloride was not the expected tertiary compound but was instead the secondary isomer, 2-chlorobicyclo(2,2,l)heptane (11), which was also obtained by adding hydrogen chloride to bicycl0(2,2,l)-%-heptene. Its structure was further proved by hydrolyzing i t to 2-hydroxybicyclo (2,2,l)heptane,better known as ,B-norcamphanol. P-Norcamphanyl ether was obtained as a by-product of the hydrolysis. The fact that the bicycloheptane yields a secondary chloride is significant since it indicates that this hydrocarbon differs from those previously studied' in that a hydrogen atom attached to a secondary carbon atom rather than one attached to a tertiary carbon atom is involved in the exchange reaction. This non-formation of the tertiary bicycloheptyl compound may be explained as being due t o the impossibility in this case of forming the intermediate tertiary carbonium ion as postulated by the mechanism of Bartlett and his co-workers.' The tertiary bicycloheptyl carbonium ion presumably cannot exist because the central carbon atom and the three carbon atoms forming bonds with it cannot be coplanar."
Experimental
Reaction of Bicyclo(Z,%,l)heptanewith &Butyl Chloride. -A solution of 52 g. (0.54 mole) of the bicycloheptane (prepared according to the directions given by Thomas) , 4 52 g. (0.56 mole) of t-butyl chloride and 25 g. of n-pentane T H x s JOIJRWAL, diluent was placed in a large test-tube of such dimensions
(1) P D Bartlett F E Condon and A Schneider 66, 1531 (1944). (2) For a description of the condensation of alkyl halides with for example, ethyleiie see L Schmerltng, abtd , 61, 1152 (1945)
(3) P. D. Bartlett and L. H. Knox, ibid., 61, 3184 (19801 (4) C. L. Thomas, Ind. E n g . Chem., 36,310 (1944).
196
LOUISSCHMERLING
(50 mm. X 350 mm.) that it could readily be cooled by immersion in a Dry Ice-acetone-bath in a quart Dewar jar. A low-temperature thermometer was suspended in the test-tube by means of a wire. The solution was cooled to about -70' and 3 g. of powdered resublimed aluminum chloride was added. The test-tube was removed from the bath and allowed to warm up while being shaken manually. Relatively 1i:tle reaction occurred until the temperature reached -5 . The temperature was maintained a t 0 to 15" during the next twenty minutes by occasional cooling. A test sample showed that the yield of chlorobicycloheptane was low. More catalyst (3 g.) was added and the intermittent shaking and cooling was continued for thirty minutes, the temperature being kept at -10 to +5". The clear yellow upper layer was then decanted from the reddish brown sludge, washed with water, dried and distilled. Besides unreacted materials and isobutane (not collevted), there was obtained 16 g. (23% of the theoretical yield based on the charge) of 2-chlorobicyclo(2,2,1)(30 heptane or 2-chloro-p-n0rcamphane,~b. p. 69-7:" mm.: or 162-163" (760 mm.); m. p. -8 to -7 ; 132013 1.4825. Only a trace of higher boiling product was obtained. 2-Chloro-8-norcamphane was previously prepared by Komppa and Beckmanna by the action of phosphorus pentachloride on 6-norcamphanol which was obtained in several steps from norcamphor. Their product boiled a t 66-67' (25 mm.) and at 160-162' (atm. pressure) and melted a t -5". An attempt was made to increase the yield of the chloronorcamphane by more careful control of the reaction conditions. &Butyl chloride (100 g., 1.08 moles) was added during fifty minutes to a stirred mixture of 100 g. (1.04 moles) of bicyclo(2,2,l)heptane; 50 g. of n-pentane and 10 g. of aluminum chloride in the conventional type of three-necked flask equipped with a dropping funnel, a mercury-sealed stirrer, and a reflux condenser. The temperature was maintained a t 0-2". Stirring was continued for one hour, after which the product was worked up in the usual manner. There was obtained 30 g. (22% of the b. p. theoretical yield) of 2-~hlorobicyclo(2,2,1)heptane, 61-62" (20 nim.); m. p. -5'; n z O ~1.4832. A mixture of this material with the product obtained by adding hydrogen chloride to bicyclo(2,2,1)-2-heptene(see below) also melted a t -5". In a third experiment, the l-butyl chloride (100 g.) was gradually added to the stirred mixture of 100 g. of bicycloheptane, 50 g. n-pentane, and 10 g. of aluminum chloride a t - 18 to - 10'. A test sample showed that not more than 5% of chloronorcamphane was formed. The reaction temperature was therefore permitted to rise to 0 and stirring was continued a t that temperature for one hour. Distillation of the washed product yielded 32 g. (255; of the theoretical yield) of 2-chlorobicyclo(2,2,1)heptane and, as in the other experiments, very little higherboiling material. Addition of Hydrogen Chloride to Bicycle( 2,2,1)-2heptene.-A stream of hydrogen chloride was bubbled in 100 through a stirred solution of 50 g. of bi~ycloheptene~ g. of technical n-pentane. The reaction temperature was kept a t -28 to -34" during the first fifteen minutes; only 5.5 g. of hydrogen chloride was absorbed, the major portion passing through unreacted. Lowering the temperature to about -70" resulted in more rapid absorption during the nest fifteen-minute period. Distillation of -__( 5 ) Chemical Abstracts nomenclature. Komppa and Beckmanne state that this and the related compounds are more correctly named as derivatives of norbornylane. (6) 3. Komppa and S. Beckmann, A n n . , 611, 172 (1934).
Vol. 68
the washed product yielded 52 g. (75%) of Z-chlorobicyclo(2,2,l)heptane, b. p. 52' (11 mm.); m. p. -5'; %*OD 1.4849. Hydrolysis of 2-Chlorobicyclo(2,2,l)heptane.-A sealed tube containing 9 g. of the chlorobicycloheptane (obtained by the reaction of bicycloheptane with t-butyl chloride), 2 g. of magnesium oxide and 100 g. of water was heated in an Ipatieff-type rotating autoclave a t 240" for four hours. Water was placed outside the sealed tube in order to prevent its bursting. The chloride was converted into a yellow crystalline solid which was taken up in ether, and distilled under reduced pressure (30 mm.). The major portion (about 4 9.) of the material sublimed to the top of the fractionating column, leaving 0.8 g. of residue in the flask. The sublimate was recovered by refluxing ethanol through the column. Water was added to the alcoholic solution, and the resulting mixture of oil and aqueous ethanol was distilled through a 14-inch total reflux fractionation column.? A mixture of oil and water distilled over a t 95'. The oil crystallized on cooling to room temperature. The crystals (2.5 g.) melted a t 120-121" and boiled a t 178-179" (in a test tube). They yielded a phenylurethan which melted a t 145", proving that the material was p-norcamphanol. Komppa and !eckmanne report that P-norcamphanol boils a t 176-177 , melts a t 123-124" 0: 127-128", and yields a phenylurethan melting a t 145-156 . The residue (0.8 9.) from the vacuum distillation was also steam distilled. Crystals melting a t 66-67" were obtained. These consisted of bicyclo(Z,Z,l)heptyl ether which has also been obtained8 as a by-product of the hydration of bicyclo(2,2,1)-2-heptene with dilute sulfuric acid. The ether crystals differed physically from the norcamphanol crystals in that they were transparent, hard, and brittle while the alcohol crystals were white and fluffy. Eighteen grams of the .chlorobicycloheptane obtained by the addition of hydrogen chloride to the bicycloheptene was hydrolyzed in a similar manner. The crystalline product was taken up in methanol (in order to remove it from the tube) and the resulting solution plus the aqueous layer and the magnesium hydroxide was distilled through the 14-inch column. A mixture of water and @-norcamphanol (8 g.) distilled over a t 95-97' and of water and dinorcamphanyl ether (4 9.) a t 98". The P-norcamphanol which melted a t 120" was further ch:racterized by means m. p. 105 . The bicycloheptyl of its 3,5-dinitroben~oate,~ ether crystals melted a t 67" and boiled a t 245-250" in a test-tube.
Summary Exchange of hydrogen for chlorine occurs when bicyclo(2,2,l)heptane is contacted with t-butyl chloride a t about 0' in the presence of aluminum chloride. The product is 2-chlorobicyclo(2,2,1)heptane rather than the expected tertiary chloride, l-~hlorobicyclo(2,2,l)heptane. Hydrolysis of the chloride yields 2-hydroxybicyclo(2,2,l)heptane (i. e., P-norcamphanol) and P-norcamphanyl ether. RIVERSIDE, ILLINOIS
RECEIVED OCTOBER 26, 1945
(7) C.L. Thomas, H S. Bloch and J Hoekstra, Ind. Eng. Chem., Anal. E d . , 10, 163 (1938). (8) H. A. Bruson and T. W. Riener, IS JOURNAL, 67, 728 (1945). (9) Alder and Rickert, A n n . , 643, 1 (1939).
